Formation of Aza-ortho-quinone Methides under Room Temperature Conditions: Cs2CO3 Effect

Daniel M. Walden, Ashley A. Jaworski, Ryne C. Johnston, M. Todd Hovey, Hannah V. Baker, Matthew P. Meyer, Karl A. Scheidt*, Paul Ha Yeon Cheong

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Since the first report of a facile, room temperature process to access aza-ortho-quinone methides (aoQMs) by Corey in 1999, this chemistry has remained dormant until our report of an enantioselective catalytic example in 2014. We report a theoretical and experimental study of the key to success behind these successful examples to enable broader exploitation of this useful intermediate. We have discovered that transformations involving the aoQM are remarkably facile with barriers <17 kcal/mol. The main difficulty of exploiting aoQM in synthesis is that they are unstable (ΔG > 30 kcal/mol), precluding their formation under mild conditions. The use of Cs2CO3 as base is critical. It provides a thermodynamically and kinetically favorable means to form aoQMs, independent of the salt solubility and base strength. The exothermic formation of salt byproducts provides a driving force (average ΔG = -30.8 kcal/mol) compensating for the majority of the inherent unfavorable thermodynamics of aoQM formation.

Original languageEnglish (US)
Pages (from-to)7183-7189
Number of pages7
JournalJournal of Organic Chemistry
Volume82
Issue number14
DOIs
StatePublished - Jul 21 2017

ASJC Scopus subject areas

  • Organic Chemistry

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